[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2008067298A1 - Le procédé de détection d'analytes chimiques et biomoléculaires et système de détection utilisant une microconsole - Google Patents

Le procédé de détection d'analytes chimiques et biomoléculaires et système de détection utilisant une microconsole Download PDF

Info

Publication number
WO2008067298A1
WO2008067298A1 PCT/US2007/085615 US2007085615W WO2008067298A1 WO 2008067298 A1 WO2008067298 A1 WO 2008067298A1 US 2007085615 W US2007085615 W US 2007085615W WO 2008067298 A1 WO2008067298 A1 WO 2008067298A1
Authority
WO
WIPO (PCT)
Prior art keywords
microcantilever
sensing surface
cantilever
sensing
change
Prior art date
Application number
PCT/US2007/085615
Other languages
English (en)
Inventor
Goutam Koley
Muhammad Qazi
Thomas Vogt
Sangmoon Park
Original Assignee
University Of South Carolina
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University Of South Carolina filed Critical University Of South Carolina
Priority to US12/442,954 priority Critical patent/US8252598B2/en
Publication of WO2008067298A1 publication Critical patent/WO2008067298A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/022—Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/44—Processing the detected response signal, e.g. electronic circuits specially adapted therefor
    • G01N29/4454—Signal recognition, e.g. specific values or portions, signal events, signatures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/01—Indexing codes associated with the measuring variable
    • G01N2291/014—Resonance or resonant frequency
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/025—Change of phase or condition
    • G01N2291/0255—(Bio)chemical reactions, e.g. on biosensors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/025—Change of phase or condition
    • G01N2291/0256—Adsorption, desorption, surface mass change, e.g. on biosensors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/04—Wave modes and trajectories
    • G01N2291/042—Wave modes
    • G01N2291/0427—Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/42—Piezoelectric device making
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/49—Method of mechanical manufacture
    • Y10T29/49002—Electrical device making

Definitions

  • Micro-electromechanical systems have been extensively used as sensors for a variety of mechanical parameters such as pressure, flow, mass, and stress. In addition, they have been used for several electrical applications, such as filters and switches in Integrated Circuits and high quality factor (high-Q) oscillators.
  • Micro-electromechanical systems MEMS
  • NEMS nano- electromechanical systems
  • Chemical sensors have widespread industrial and environmental applications including toxic gas sensing, process flow monitoring, and pollution control.
  • Bio-molecule sensors on the other hand are extremely useful for label-free detection in lab-on-a-chip type applications, bio- hazard detection for counter-terrorism, and homeland security.
  • the microcantilever used in a scanning probe microscope (SPM) in non- contact or tapping modes is essentially a MEMS device.
  • SPM scanning probe microscope
  • the advantage of using a microcantilever in measurements such as in a SPM include high quality factors of such oscillatory systems, easy batch fabrication using standard lithographic techniques, and a base material (commonly Si) with tunable electrical properties.
  • base material commonly Si
  • MEMS/NEMS detection system an electrical signal is converted to mechanical oscillations of a resonator, which under the influence of external agents (analyte molecules), changes its resonance characteristics. This change is then converted back into an electrical signal enabling detection.
  • MEMS based sensing is usually preferred due to its extremely high sensitivity resulting from its very high quality factor (in the range of 10 5 - 10 7 in vacuum), which greatly exceeds that of its electrical counterparts.
  • the power consumed by these sensors is very low, so a large array of these sensors can be packed together with very low power dissipation, for lab-on-a-chip or multi-functional sensing applications.
  • the barrier potential change is related to the current, the latter can be measured to detect the attachment of the target molecules.
  • the external agents analyte molecules
  • the surface of the microcantilever must be cleaned (i.e., remove any attached analytes from the surface) or replaced.
  • replacing the microcantilever after each use increases the cost dramatically, not to mention being wasteful.
  • the present invention is directed to development of novel chemical and bio-molecular sensors based on a reusable microcantilever system.
  • the system can include a microcantilever device having a resonating element positioned within working proximity of a counter electrode.
  • the counter electrode includes a sensing surface (e.g., graphite or a nanostructure) configured to bond to an analyte.
  • the detection device is configured to monitor the movement of the resonating element.
  • the microcantilever device can be positioned within a vacuum.
  • the sensing surface can include a plurality of different functionalized electrodes.
  • the microcantilever can be configured to move across the sensing surface in a plane that is parallel with the sensing surface such that the microcantilever can be positioned in working proximity to each of the differently functionalized electrodes.
  • the present invention is directed to a method of forming a detection system for detecting the presence of an analyte.
  • a microcantilever device comprising a resonating element is positioned within working proximity of a sensing surface on a counter electrode.
  • a detection device configured to monitor the movement of the resonating element.
  • the present invention is directed to a method of detecting the presence of an analyte.
  • the method includes providing a detection system having a microcantilever device positioned within working proximity to a counter electrode.
  • the microcantilever device comprises a resonating element
  • the counter electrode comprises a sensing surface configured to bond to an analyte.
  • the change in surface work function or charge configurations of the sensing surface is measured or detected utilizing a detection device configured to monitor the movement of the resonating element.
  • Figure 1 shows a prospective view of an exemplary detection system of the present invention.
  • Figure 2 depicts a side view of the exemplary detection system of Fig. 1.
  • Figure 3 depicts a schematic diagram of a cantilever resonator based chemical/ bio-molecule sensor.
  • Figure 4 depicts an exemplary setup for a gas sensing detection system.
  • Figure 5 shows NO 2 sensing using an In 2 O 3 film annealed in 600 0 C in air.
  • Figure 6 shows NO 2 sensing using an In 2 O 3 film annealed in 1000 0 C in air.
  • Figure 7 shows NO 2 sensing using an In 2 O 3 film annealed in 1000 0 C in air.
  • Figure 8 shows NO 2 sensing comparing In 2 O 3 films annealed in 600°C and 1000°C in air.
  • Figure 9 shows a conceptual diagram of the chemical and bio-molecule sensor with individually addressable test (analyte) electrodes where the Translation Stage can move the substrate in x and y directions to bring the desired electrodes under the cantilever for sensing.
  • Figure 10 shows a schematic diagram of the measurement set up.
  • the cantilever has only a small overlap with the stripe metal electrode to minimize parasitic capacitances.
  • the cantilever is excited by the piezo at a frequency ⁇ 0 , and by the applied biases at a frequency ⁇ , slightly different from ⁇ 0 .
  • Figure 11 shows (a) variation of the beat oscillation amplitude of the cantilever as a function of dc bias (note that this amplitude corresponds to the actual slow movement of the piezo-resonator and hence of the cantilever, which is caused by the feedback mechanism to maintain a constant amplitude of oscillation) and (b) variation of the oscillation amplitude as a function of ac bias.
  • the sensitivity is calculated as the ratio of the change in oscillation amplitude to a change in dc bias.
  • Figure 12 shows (a) surface potential rise and fall transients as the 1000 ppm hydrogen is switched on and off and (b) comparison of the surface potential transients for 1000 ppm hydrogen and pure nitrogen, as they are switched on and off.
  • Figure 13 shows a comparison of 600 ppb NO 2 sensing using graphene layer produced by abrasion of pencil graphite.
  • Figure 14 shows a comparison of the change in current flow between two contacts established on the sensing films (a) graphene produced by abrasion of pure graphite, and (b) graphene produced by abrasion of pencil graphite, as 8 ppm NO 2 flow is switched ON and OFF.
  • the present disclosure is directed to methods of detecting analytes using a microcantilever system.
  • the microcantilever system generally includes micro- or nano-sized elements that can be electrostatically driven to resonance. More specifically, utilizing the disclosed devices and methods, direct electronic detection of the resonant frequency, changes of the resonant frequency, and associated phase signal of a micro- or nano-sized element can be utilized to measure the presence of a targeted analyte.
  • the presently disclosed methods and systems can facilitate the formation of economical, portable NEMS and MEMS devices suitable for use in practical, real- world applications.
  • the disclosed methods can be utilized with other devices as well, for instance, the disclosed methods can be utilized in development of high quality electronic filters as well as other high quality (high Q factor) electronic devices.
  • the microcantilever system includes a microcantilever that can be reused a plurality of times.
  • the detection system and methods of the present invention generally include a microcantilever device positioned in working proximity to a sensing surface. By keeping the sensing surface separate from the microcantilever, the system can be reused simply by replacing or cleaning the separate sensing surface without the need for a new microcantilever device. Additionally, the sensing surface can be replaced (so as to refresh or to detect a different targeted analyte) without having to disturb the microcantilever device.
  • the detection system of the present invention can utilize a non- contact microcantilever device. That is, the surface of the microcantilever (e.g., the surface of the resonating beam) does not bond or otherwise attach to an analyte or other chemical. Thus, the microcantilever device, including the resonating beam, can be kept in pristine condition during and even after repeated use. Additionally, through the use of a non-contact microcantilever device, there is no need to functionalize the surface of the resonating beam in a particular manner depending on the targeted analyte. Thus, there can be more uniformity in the manufacture of each microcantilever device.
  • a detection system 10 having a microcantilever device 12 with a resonating 14 and a sensing surface 16. Although shown as a resonating beam 14 having a rectangular shape, it should be understood that any other shaped resonating element can be utilized in accordance with the present invention. Both the microcantilever device 12 and the sensing surface 16 will be discussed in greater detail below.
  • the resonating beam 14 is positioned within working proximity (measured by the distance d) to the sensing surface 16, so as to induce a charge on the resonating beam 14 while remaining in a non-contact mode.
  • the preferred gap distance between the sensing surface 16 and the resonating beam 14 can vary, and can depend, for instance, upon the nature of the atmosphere surrounding the system and on the geometric relationship between the microcantilever device 12 and the sensing surface 16. In general, however, the intervening distance between the resonating beam 14 and the sensing surface 16 can be at least enough so as to ensure no contact between the sensing surface 16 and the resonating beam 14 at resonance, while ensuring the capability of establishing a capacitance driven electrostatic force on the microcantilever device 12.
  • a voltage is applied to the detection system 10, so as to induce a modulated electrostatic force on the cantilever.
  • the detection system 10 can also include a signal generator 18, shown as an ac voltage generator.
  • the voltage applied to the sensing surface 16 can induce an electrostatic force on the resonating beam 14, which, at the appropriate parameters, can force the resonating beam 14 into resonance.
  • the resonating beam 14 is positioned above the sensing surface 16 such that the resonating beam 14 and the sensing surface 16 are substantially parallel to each other.
  • any other configuration e.g., tip-to- tip
  • tip-to- tip could be utilized in accordance with the present invention.
  • the microcantilever device 12 can include one or more micro-sized or nano- sized elements.
  • the devices can utilize one or more micro-sized beams, such as the resonating beam 14 shown in Figs. 1-2.
  • micro-sized beams can be classified as those having micrometer dimensions, e.g., greater than about 1 micrometer ( ⁇ m) in width and/or thickness.
  • micro-cantilevers of the present invention can have a length dimension less than about 500 ⁇ m, for instance between about 90 ⁇ m and about 350 ⁇ m and a width dimension less than about 50 ⁇ m, for instance between about 10 ⁇ m and about 50 ⁇ m.
  • Nano-sized beams generally include those elements having width and/or thickness dimensions less than the micro-sized devices (e.g., less than about 1 ⁇ m).
  • nano-sized elements of the invention can have a width and/or thickness dimension less than about 500 nm.
  • Nano-sized elements can, however, have a length in the micrometer range.
  • one exemplary nano-cantilever of the invention can have a generally circular cross- section of between about 1 nm and about 200 nm in diameter, and a length in the micrometer range, for instance greater than about 5 ⁇ m.
  • the beams of the devices can have any geometric shape and can have an aspect ratio (UD) greater than about two.
  • UD aspect ratio
  • the presently disclosed methods and devices are equally applicable to a beam provided in other orientations.
  • the invention is also directed to devices in which the disclosed beam is clamped at both ends, i.e., a double- clamped beam.
  • the presently disclosed invention encompasses any micro- or nano-sized element that can be electrostatically driven into resonance.
  • the elements of the disclosed devices can generally be formed of any material including a suitable conductive or semi-conductive material at least at the surface of the element.
  • an element can be formed of a non-conductive base substrate that has been coated with a conductive outer layer.
  • Fabrication materials and techniques for forming many structures suitable for use in the presently disclosed devices are generally known to those of ordinary skill in the art.
  • materials encompassed by the invention include metallic nanowires, gallium arsenide/aluminum arsenide structures, nanocrystalline diamond films, and materials based upon silicon including, but not limited to, silicon on insulator structures, silicon carbide on silicon structures, aluminum nitride on silicon structures, and amorphous silicon nitride structures.
  • the elements of the disclosed devices can be nanostructures, and in one particular embodiment, carbon-based nanostructures.
  • carbon-based nano-cantilevers of the disclosed devices can be formed from nanotubes, including single-walled nanotubes (SWNT) and multi- walled nanotubes (MWNT), nanobelts, nanorods, nanowires, nanocoils, and the like.
  • the elements can be formed of more than one nanostructure in combination, for example, a bundle of nanotubes, or a stack of nanobelts, or even combinations of two or more structures of different shapes.
  • Nanostructures of the invention are not limited to carbon-based nanostructures, however, and nanostructures formed of other material can be utilized.
  • nanostructures etched from silicon or including any other suitable conductive or semi-conductive material at the surface can be utilized.
  • other resonating structures such as beams attached at both ends can also be used for the non-contact detection.
  • the elements of the disclosed devices can be formed according to any known formation method and of any suitable material.
  • carbon-based nano-cantilevers of the invention can be formed via physical evaporation methods such as vapor-liquid-solid (VLS) processes, chemical vapor deposition (CVD) methods, catalyst assisted processes, processes involving electric arc gas discharge, pulsed laser ablation techniques, or by simple mechanical abrasion, as are generally known to those of ordinary skill in the art.
  • VLS vapor-liquid-solid
  • CVD chemical vapor deposition
  • catalyst assisted processes processes involving electric arc gas discharge, pulsed laser ablation techniques, or by simple mechanical abrasion, as are generally known to those of ordinary skill in the art.
  • the microcantilever device can be positioned in a vacuum.
  • a vacuum By positioning the microcantilever device in a vacuum, any potential contact between the microcantilever and any environmental contaminants are avoided. Thus, false readings can be minimized.
  • the quality factor of the resonance increases dramatically in vacuum (usually 100-1000 times) causing exceptional sensitivity toward molecules that can absorb on the functionalized surface outside of the vacuum enclosure.
  • the sensing surface can be constructed of any suitable material that has an affinity for the targeted analyte.
  • One of ordinary skill in the art would be able to functionalize the sensing surface to attract and bond (e.g., covelent bond, ionic bond, hydrogen bond, etc.) to the targeted analyte(s).
  • the sensing surface acts as a counter electrode to the microcantilever to complete the detection system circuit.
  • the sensing surface itself may have only marginal conductivity, the sensing surface can be located on a more conductive material, such as a metal electrode or a semiconductor attached to an electrode. In one particular embodiment, the sensing surface can be applied on semiconductor substrate.
  • the sensing surface when sensing nitrogen oxides, can be silicon or silicone oxide.
  • Gases such as NOx (where x is 1 or 2), NH 3 , and H 2 S have the property of releasing or accepting electrons when in contact with transition metal oxides, such as In 2 O 3 , SnO 2 and ZnO.
  • the reference electrodes i.e. the counter electrode
  • the surface potential changes can be measured at room temperature and/or at elevated temperatures.
  • the present inventors have discovered that the use of thin graphite films is suitable for sensing the above-mentioned gases.
  • Thin films of graphite can be produced economically on a variety of substrates, including metals, semiconductors and insulators.
  • the term "graphite” is meant to encompass graphite in any form.
  • nanostructured graphite (NG) can be used as the functionalization layer, which can be deposited easily and inexpensively on a variety of substrates by simple mechanical abrasion on the substrate or by coating powders (comprising nanoscale particles) of graphite.
  • the NG layer can mostly include of crystalline graphene films with nanoscale dimensions, creating a large surface area.
  • Graphene films which consist of a single layer of carbon atoms are sensitive to a variety of molecules. For electron poor gases such as NO 2 , detection down to a single molecular level is possible. Graphene is a unique material that is truly two-dimensional, and has electron and hole mobilities of several thousands at room temperature with carrier concentration reaching as high as mid 10 13 cm "2 .
  • graphene is ambipolar (both electrons and holes carry current simultaneously), with a slight overlap of a few tens of meV between the conduction and valence band edges. Therefore, it is relatively easy to make a few layer graphene (FLG) film p-type or n- type (holes or electrons as the net carriers) by applying appropriate bias between the graphene film and a metal electrode separated by an insulator (such as SiO 2 ).
  • FLG graphene
  • the graphene sensing surface can be made by coating graphene layer onto a grounded substrate.
  • the process used to create these films in this case is not (1) the more commonly used physical deposition using sputtering or pulsed laser deposition or even (2) the economically attractive chemical deposition technique, which lends itself to commercialization.
  • the process used to create these films involves applying graphite (such as from a readily available pencil) onto a substrate such as metal or even paper. Of course, any method of applying graphite to form the sensing surface can be utilized.
  • the sensing surface can include nanostructures, such as carbon-based nanostructures.
  • nanostructures such as carbon-based nanostructures.
  • the ability of carbon nanostructures to quickly adsorb materials is of benefit to the disclosed devices in certain sensing applications.
  • carbon-based sensing surfaces can be formed from nanotubes, including single-walled nanotubes (SWNT) and multi-walled nanotubes (MWNT), nanobelts, nanorods, nanowires, nanocoils, and the like.
  • Nanostructures of the invention are not limited to carbon-based nanostructures, however, and nanostructures formed of other material can be utilized.
  • nanostructures etched from silicon or including any other suitable conductive (such as Pt or Pd nanoparticles for hydrogen sensing) or semi-conductive material at the surface can be utilized.
  • FIG. 3 A generic diagram of MEMS/NEMS based sensing is shown in Figure 3. As can be seen, the electrical signal is converted to mechanical oscillations, which are then converted back to electrical signal to take advantage of high sensitivity and low power requirements of the mechanical resonator.
  • the sensitivity of the cantilever sensor is determined with respect to changes in surface potential and charge.
  • the total force on the cantilever, F tot (which in turn controls the sensitivity) is given by:
  • C is the tip sample capacitance and ⁇ is the difference in work function of the tip and the sample.
  • the different parameters affecting the sensitivity such as, resonator-reference electrode distance, ac voltage magnitude, area of the resonator, and its quality factor, can be systematically varied.
  • the sensing technique disclosed herein is based on the change in surface work function of the sensing surface due to adsorption of the target molecules.
  • the present inventors have discovered, through experiments conducted with commercial probes with triangular and rectangular cross-sections and with various stiffness and quality factors, that the surface potential sensitivity of the sensor can be down to one microvolt or less.
  • the sensitivity of the cantilever to surface charge also depends on the factors mentioned herein.
  • a change in the surface work function of the sensing surface results in the amplitude of resonance (R) of the microcantilever, which can be detected by any detection device or method.
  • the cantilever displacement can be detected, in one particular embodiment, using a laser and photodetector based transduction mechanism.
  • the displacement can be detected using a piezo-resistive cantilever, which will significantly reduce the cost of manufacturing these sensors.
  • the resistance of a piezo-resistive element is proportional to its displacement, which will be used to detect the change in deflection of the cantilever caused by the change in surface potential.
  • the change in capacitance between the cantilever and the reference electrode which changes with distance, can be measured to detect the cantilever tip displacement.
  • the current detection method has the advantage of using a resonating cantilever for detection such that very low surface potential changes and charges can be detected, since the sensitivity of the cantilever resonator depends not only on the Q-factor, but also the cantilever-sample distance (which can be easily controlled), and the area of cantilever (unlike the mass detection where the sensitivity depends only on the Q-factor, or the chem-FET where the current change is fixed depending on the surface potential change).
  • the presently disclosed methods it is possible to approach single molecule detection capability, and easily surpass the detection limit of the other techniques, such as those based on mass changes or surface stress changes, by orders of magnitude.
  • the high sensitivity of the microcantilever resonator sensors with regard to surface potential changes allows the detection device to apply the sensing methodology to detect less than 1000 ppm hydrogen with very low response time, such as about 6 ppm of hydrogen. Likewise, less than 100 ppb of nitrogen, such as about 60 ppb of nitrogen, can be detected.
  • surface potential change caused by adsorbed analyte molecules
  • the minimum surface potential change as well as the minimum surface charge that is detectable by the displacement of a cantilever sensor is described herein.
  • Sensors based on surface potential change are more sensitive than amperometric methods commonly used, since the signal can be enhanced by optimizing four independent parameters: (1 ) the distance between the probe and the reference electrode, (2) applying dc voltage simultaneously with the ac voltage V ac to the resonator, (3) the quality factor, and (4) the area of the probe. The charge is affected by the first three parameters.
  • Figure 4 shows an exemplary sensing experiment.
  • the cantilever displacement in that setup is detected using a laser.
  • displacement can be detected using a piezoelectric or piezoresistive cantilever.
  • the ac current flowing through a piezoelectric element is proportional to its displacement.
  • SILAR Successessive Ionic Layer Adsorption and Reaction
  • Pb(OAc) 2 3H 2 O, Zr(O ⁇ Pr) 4 OH and Ti(O n Bu) 4 solutions can be used to create PZT films on the cantilevers in a cheap and industrially relevant process. This will reduce the costs of manufacturing suck sensors considerably.
  • an n- dimensional signature of a particular type of analyte molecule can be determined with respect to the surface potential changes in an array of n different functionalized electrodes as shown in Figure 7.
  • Electrodes containing special coating (such as CNT, Au, or transition metal oxides such as In 2 O 3 , WO 3 , SnO 2 ) for selectively interacting with specific molecules in air or liquid, can be fabricated on an insulating substrate (called a sensor cassette).
  • the sensor cassette can be moved in x and y directions, so that a particular electrode can be positioned under the fixed cantilever (oscillating in the z-direction).
  • the incoming molecules will interact with the specific electrodes, and produce changes in chemical potential, which will be measured by the cantilever, and subsequent circuitry.
  • the presence of different analyte molecules in a gas mixture can be sensed by using a computer, which can be interfaced with the sensor to obtain the n-dimensional data for a given gas mixture, and which can be compared against a database containing the signatures for a spectrum of target analyte molecules.
  • the displacements of the individual cantilevers can be determined by measuring the ac current of a piezoelectric or piexoresistive film deposited on the cantilevers.
  • Example 1 illustrate the development of sensors using chemical deposition as disclosed herein and is not meant to limit the scope of the invention:
  • the magnitude of the coulombic force of attraction is orders of magnitude higher (for small distances) than any other force.
  • a special fluid cell can be used for testing bio-molecules in fluid media.
  • the cell can be modified slightly (replacing the O-ring and the rubber base with inert materials) so that toxic chemical molecules in gaseous form, such as NOx, NH 3 , H 2 S, and hydrogen (due to its combustible properties) can be tested.
  • toxic chemical molecules in gaseous form such as NOx, NH 3 , H 2 S, and hydrogen (due to its combustible properties) can be tested.
  • the initial focus was on studying the interaction between hydrogen and nitrogen oxides with Palladium and Platinum coated substrates.
  • Gases such as NOx, NH 3 , H 2 S have the property of releasing or accepting electrons when in contact with transition metals such as In 2 O 3 , SnO 2 and ZnO.
  • the reference electrodes are coated with these materials and the surface potential changes are measured at room temperature and at elevated temperatures.
  • Example 2 Disclosed herein is an NO 2 sensor developed using the above outlined principles by coating In 2 O 3 , SnO 2 and mixtures of In 2 O 3 and SnO 2 onto a ground substrate coated with a functionalized film.
  • the process used to create these films is not the more commonly used physical deposition using sputtering or pulsed laser deposition but an economically attractive chemical deposition technique (SILAR), which lends itself to commercialization.
  • SILAR economically attractive chemical deposition technique
  • Measurements were carried out with uncoated Si cantilevers, as well as ones coated with 10 - 15 nm Pt, using a commercial atomic force microscope (AFM) set up.
  • the resonance frequencies of the cantilevers were -20 KHz, and the spring constant -0.08 N/m.
  • the cantilevers were made to oscillate at a frequency ⁇ , very close to the resonance frequency ⁇ o, using an ac (frequency ⁇ o) and a dc bias applied to the cantilever.
  • the amplitude of oscillations of the cantilever was detected by creation of amplitude modulation of the cantilever (through formation of beats) by simultaneous application of another periodic excitation using the piezo resonator of the AFM at frequency ⁇ 0 (see
  • the beat frequency ⁇ - ⁇ o was kept low ( ⁇ 2.5 Hz) so that the AFM feedback module can easily respond to it, and move the cantilever accordingly. Since this would be difficult to detect otherwise, the change in oscillation amplitude was detected by the AFM feedback mechanism, which moves the piezo-positioner up and down in response to changes in amplitude of the oscillations.
  • the cantilever was positioned above a striped Au pattern (reference electrode biased to ground) with small overlap (-30 ⁇ m) between the cantilever and the reference electrode (see Figure 10). This ensured that the parasitic capacitance associated with the cantilever assembly remained low.
  • the amplitude of beat oscillations is plotted against dc bias in Figure 11a (for a constant ac bias of 9 V amplitude), which shows the sensitivity to be -400 nm/mV.
  • the variation of sensitivity with ac bias is plotted in Figure 11 b, and we can see that the sensitivity increases almost linearly with increase in ac bias, and reaches a value -306 nm/mV, for an ac bias of amplitude 9V.
  • the tip-sample distance for these measurements was determined to be >10 ⁇ m.
  • the rms noise for these measurements was determined from a scan taken with constant dc and ac biases, to be -20 nm.
  • the high noise is due to the high AFM feedback gain used, the noise in the biases, and thermal noise. Nevertheless, the minimum dc bias change that can be sensed using this setup for a 9V ac bias applied is found to be about 50 ⁇ V. This can be easily improved by reducing the cantilever-sample distance, as well as increasing the ac bias. Increasing the cantilever area and Q-factor, and reducing the spring constant, will also proportionally increase the sensitivity. The sensitivity of normal Kelvin probe microscopy where the cantilever is excited (with the ac bias) far from the resonance frequency is usually a few mV.
  • the cantilever sensor was used to detect 1000 ppm hydrogen by coating the cantilever with platinum.
  • Platinum was chosen since it has the unique property of adsorbing hydrogen.
  • the mechanism of hydrogen's interaction with platinum, especially in terms of work function change under ambient conditions, is not well understood. Very few studies have been reported, and mostly under high vacuum conditions. It is contended from these studies that the change in work function (magnitude and sign) depends on the surface coverage of hydrogen on the platinum surface.
  • the cantilever based potentiometric sensor described here can serve as a very sensitive measurement tool (much more sensitive than conventional Kelvin probe, due to Q-factor enhancement as discussed earlier) for changes in surface potential due to adsorbed or attached molecules on exposed surfaces.
  • the change in surface potential when 1000 ppm hydrogen (balance nitrogen) is flown over the Pt coated cantilever is shown in Figure 12a.
  • the surface potential change was calculated as the ratio of the change in oscillation amplitude (nm) and sensitivity (nm/mV). Since the maximum oscillation amplitude possible is only 4 ⁇ m in the current system, the applied dc bias was changed manually to reset the amplitude to a predetermined low value, each time the 4 ⁇ m amplitude was reached.
  • the sensing thin films of In 2 O 3 and SnO 2 on Si substrates were prepared using aqueous solutions of ln(NO 3 ) 3 xH 2 O, InCI 3 XH 2 O, SnCI 2 XH 2 O, and NaOH.
  • the Si substrates were previously fired in a furnace at 1000 0 C for 30 min.
  • the In 2 O 3 and SnO 2 were fabricated by SILAR (Successive Ionic Layer Adsorption and Reaction) and SDH (Successive Dipping Heating) deposition methods.
  • SILAR Successessive Ionic Layer Adsorption and Reaction
  • SDH Successessive Dipping Heating
  • the dipping sequence in an In-containing solution, water, an NaOH solution, and water was 3 seconds, 6 seconds, 3 seconds, 6 seconds and in a Sn-containing solution, ethanol, water, ethanol, it was 3 seconds, 6 seconds, 3 seconds, 6 seconds established to obtain In 2 O 3 and SnO2 films respectively.
  • the substrate was successively immersed in In or Sn - containing alcohol solutions and a heating zone (about 50 0 C) for 1 second and 20 seconds for In 2 O 3 or 10 seconds for SnO 2 .
  • the procedures of dipping and heating were performed at the speed of about 1 mm/second.
  • the coated films were directly annealed in air at 600, 800, 1000, or 1100 0 C in a preheated box furnace.
  • Figure 5 reveals that with In 2 O 3 films made in the above mentioned process and annealed in air at about 600 0 C, NO 2 can be detected and that the signal can be enhanced by increasing V ac .
  • the NO 2 was diluted with Ar to a concentration of 10Oppm for these experiments.
  • annealing the SILAR film at about 1000 0 C in air results in an In 2 O 3 film that allows the detection of NO 2 at a faster rate and at much lower concentrations, as evidenced by the larger change in cantilever displacement.
  • the other experimental conditions used were a gas containing 100 ppm of NO 2 and a flow rate of 50 ml/minute.
  • the response time of the sensor can be reduced to a few seconds after optimization as shown in Figure 7, where the actual surface potential variation in response to NO 2 is measured.
  • the graphene films are made through mechanical exfoliation of graphite (from, for example, either a pencil or a piece of carbon) onto a rough substrate.
  • Figure 13 shows the fast rise and fall time of the surface work function which is registered when exposed to NO 2 .
  • the fall-off indicates that the surface saturates after multiple exposures.
  • the graphene surface can be reactivated using nitrogen as a flush gas.
  • the detection levels realized allow us to extend this type of NO 2 sensor into the low part-per-billion range.
  • This invention presents the opportunity to develop very inexpensive sensors, e.g. NO 2 sensors, in the part-per-billion range where the graphene sensing surface can be discharged after a measurement due to its low cost. This would prevent the long time degradation of such a surface due to humidity and exposure to other gases and provide a clean and activated surface at the beginning of each measurement.
  • very inexpensive sensors e.g. NO 2 sensors

Landscapes

  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Acoustics & Sound (AREA)
  • Engineering & Computer Science (AREA)
  • Signal Processing (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)

Abstract

L'invention concerne d'une manière générale des procédés et des systèmes de détection d'analytes au moyen d'un système de microconsole. Ce système de microconsole comprend d'une manière générale des éléments de taille micrométrique ou nanométrique qui peuvent être mis en résonance par électricité statique. Des dispositifs et des procédés de l'invention, la détection électronique directe de la fréquence de résonance, des changements de fréquence de résonance et le signal de phase associé d'un élément de taille micrométrique ou nanométrique peuvent être utilisés pour mesurer la présence d'un analyte ciblé. La surface de la microconsole (par exemple la surface de la poutre résonnante) ne se lie pas ou n'attache pas à un analyte ou à d'autres composés chimiques. Ainsi, le dispositif de microconsole comprenant la poutre résonnante, peut-être conservé en parfait état pendant et même après une utilisation répétée.
PCT/US2007/085615 2006-11-27 2007-11-27 Le procédé de détection d'analytes chimiques et biomoléculaires et système de détection utilisant une microconsole WO2008067298A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/442,954 US8252598B2 (en) 2006-11-27 2007-11-27 Method of sensing chemical and bio-molecular analytes and sensing system using a microcantilever

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US86122606P 2006-11-27 2006-11-27
US60/861,226 2006-11-27
US92141907P 2007-04-02 2007-04-02
US60/921,419 2007-04-02
US92205107P 2007-04-05 2007-04-05
US60/922,051 2007-04-05

Publications (1)

Publication Number Publication Date
WO2008067298A1 true WO2008067298A1 (fr) 2008-06-05

Family

ID=39468265

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/085615 WO2008067298A1 (fr) 2006-11-27 2007-11-27 Le procédé de détection d'analytes chimiques et biomoléculaires et système de détection utilisant une microconsole

Country Status (2)

Country Link
US (1) US8252598B2 (fr)
WO (1) WO2008067298A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011143324A1 (fr) * 2010-05-11 2011-11-17 Positiveid Corporation Système de capteur moléculaire sans fil et procédé associé

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10191082B1 (en) * 2007-01-30 2019-01-29 Victor B. Kley Carbon nanotube probes and structures and methods of measurement
US8441361B2 (en) * 2010-02-13 2013-05-14 Mcallister Technologies, Llc Methods and apparatuses for detection of properties of fluid conveyance systems
US8312759B2 (en) * 2009-02-17 2012-11-20 Mcalister Technologies, Llc Methods, devices, and systems for detecting properties of target samples
JP5813966B2 (ja) * 2011-03-03 2015-11-17 株式会社日立ハイテクサイエンス 変位検出機構およびそれを用いた走査型プローブ顕微鏡
CN102849961B (zh) * 2011-07-01 2016-08-03 中央研究院 在基板上成长碳薄膜或无机材料薄膜的方法
US20130047710A1 (en) * 2011-08-26 2013-02-28 Purdue Research Foundation Nonlinear, bifurcation-based mass sensor
US9772305B2 (en) 2011-09-15 2017-09-26 Arizona Board Of Regents On Behalf Of Arizona State University System and method for small molecule detection
WO2013052111A1 (fr) * 2011-10-03 2013-04-11 Trek, Inc. Procédé et dispositif de déplacement d'un capteur à proximité d'une surface
US20130214875A1 (en) 2012-02-16 2013-08-22 Elwha Llc Graphene sheet and nanomechanical resonator
GB201321429D0 (en) * 2013-12-04 2014-01-15 Isis Innovation Sensor
US10266397B2 (en) * 2014-08-13 2019-04-23 University Of South Carolina III-V nitride resonate structure based photoacoustic sensor
US9995719B2 (en) * 2014-08-20 2018-06-12 Massachusetts Institute Of Technology Methods and devices for selective deposition of materials including mechanical abrasion
US8981346B1 (en) 2014-09-30 2015-03-17 The United States Of America As Represented By The Secretary Of The Navy Capacitive-based graphene sensor
US10191004B2 (en) 2014-10-21 2019-01-29 University Of South Carolina Microcantilever based selective volatile organic compound (VOC) sensors and methods
WO2017008164A1 (fr) * 2015-07-13 2017-01-19 Intrepid Visions Inc. Systèmes et procédés pour actionnement de micro-levier par excitation de base
IL258100B2 (en) * 2015-09-14 2023-04-01 Essenlix Corp Apparatus and system for collecting and analyzing condensed vapor, especially condensed exhalation, and methods for using the same
EP3431982A1 (fr) * 2017-07-18 2019-01-23 Nanosurf AG Microporte-à-faux
US10900927B2 (en) 2018-03-21 2021-01-26 University Of South Carolina Graphene field effect transistors for detection of ions
JP7345763B2 (ja) * 2018-10-05 2023-09-19 株式会社カネカ 炭素系物質振動子、並びにこれを備えたセンサー素子及び生体由来物質検出装置
US11187663B2 (en) * 2019-02-11 2021-11-30 California Institute Of Technology Highly-multiplexed NEMS-array readout system based on superconducting cavity optomechanics

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4605626A (en) * 1985-05-01 1986-08-12 Rohrback Technology Corporation Electrochemical system with rotating electrode/sparger assembly
US5494831A (en) * 1993-08-30 1996-02-27 Hughes Aircraft Company Electrochemical immunosensor system and methods
US20040115711A1 (en) * 2002-09-24 2004-06-17 Xing Su Detecting molecular binding by monitoring feedback controlled cantilever deflections
US20040194534A1 (en) * 2002-06-03 2004-10-07 Porter Timothy L. Hybrid microcantilever sensors
US20060255790A1 (en) * 2005-02-14 2006-11-16 Clemson University Method and apparatus for detecting resonance in electrostatically driven elements

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4605626A (en) * 1985-05-01 1986-08-12 Rohrback Technology Corporation Electrochemical system with rotating electrode/sparger assembly
US5494831A (en) * 1993-08-30 1996-02-27 Hughes Aircraft Company Electrochemical immunosensor system and methods
US20040194534A1 (en) * 2002-06-03 2004-10-07 Porter Timothy L. Hybrid microcantilever sensors
US20040115711A1 (en) * 2002-09-24 2004-06-17 Xing Su Detecting molecular binding by monitoring feedback controlled cantilever deflections
US20060255790A1 (en) * 2005-02-14 2006-11-16 Clemson University Method and apparatus for detecting resonance in electrostatically driven elements

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011143324A1 (fr) * 2010-05-11 2011-11-17 Positiveid Corporation Système de capteur moléculaire sans fil et procédé associé
US9011333B2 (en) 2010-05-11 2015-04-21 Veriteq Acquisition Corporation Wireless molecular sensor system and process

Also Published As

Publication number Publication date
US8252598B2 (en) 2012-08-28
US20100173422A1 (en) 2010-07-08

Similar Documents

Publication Publication Date Title
US8252598B2 (en) Method of sensing chemical and bio-molecular analytes and sensing system using a microcantilever
Volodin et al. Coiled carbon nanotubes as self-sensing mechanical resonators
US8120448B2 (en) High frequency nanotube oscillator
US7598723B2 (en) Method and apparatus for detecting resonance in electrostatically driven elements
JP5393555B2 (ja) 流動媒体内の特定粒子を原位置で検出するための微小デバイスと動作方法
US20020167374A1 (en) Pattern-aligned carbon nanotube growth and tunable resonator apparatus
EP1645871A1 (fr) Transistor a electron unique, transistor a effet de champ, capteur et son procede de production, et procede de detection
US8236569B2 (en) Multi-dimensional integrated detection and analysis system (MIDAS) based on microcantilvers
US20120068156A1 (en) InN Nanowire Based Multifunctional Nanocantilever Sensors
Lefèvre et al. Scaling law in carbon nanotube electromechanical devices
WO2005034206A2 (fr) Fonctionnalisation selective de bouts de nanotubes de carbone permettant la fabrication de nouvelles classes de detection nanometrique et d'outils de manipulation
Bayerl et al. Three‐dimensional Kelvin probe microscopy for characterizing in‐plane piezoelectric potential of laterally deflected ZnO micro‐/nanowires
CN101821195A (zh) 包括纳米结构的三维纳米器件
US8384372B1 (en) Non-linear electrical actuation and detection
RU2349542C1 (ru) Наноэлектромеханическая структура (варианты) и способ ее получения (варианты)
JP5373284B2 (ja) ねじれ共振モードにおいて電気的な特性を測定するための方法及び装置
Hao et al. A high-Q length-extensional bulk-modemass sensor with annexed sensing platforms
Darbari et al. Branched carbon nanotubes to realize a novel capacitive sensor and actuator device
WO2009083720A1 (fr) Détection d'ionisation
O’Shea et al. Out-of-plane electrostatic actuation of microcantilevers
KR102571648B1 (ko) 금속-칼코게나이드 나노 튜브 기반 전기 기계식 공진기
Khanna Frontiers of nanosensor technology
Sadeghian et al. Some considerations of effects-induced errors in resonant cantilevers with the laser deflection method
Stavrov et al. Self-sensing cantilevers with nano-laminated Dielectric-Metal-Dielectric resistors
Schwender Mass sensing with graphene and carbon nanotube mechanical resonators

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07864823

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2094/KOLNP/2009

Country of ref document: IN

122 Ep: pct application non-entry in european phase

Ref document number: 07864823

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 12442954

Country of ref document: US